Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications
被引:41
作者:
Balkhi, M. Y.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Balkhi, M. Y.
Trivedi, A. K.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Trivedi, A. K.
Geletu, M.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Geletu, M.
Christopeit, M.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Christopeit, M.
Bohlander, S. K.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Bohlander, S. K.
Behre, H. M.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Behre, H. M.
Behre, G.
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机构:Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
Behre, G.
机构:
[1] Univ Halle Wittenberg, Bone Marrow Transplantat Sect, Dept Internal Med Hematol & Oncol 4, State Ctr Cell & Gene Therapy, D-06097 Halle, Germany
acute myeloid leukaemia;
proteomics;
post-translational modification;
mass spectrometry;
D O I:
10.1038/sj.onc.1209689
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Acute myeloid leukaemia (AML) is characterized by specific cytogenetic aberrations that are strong determinants of prognostic outcome and therapeutic response. Because the pathological outcome of AML patients with cytogenetic abnormalities differs considerably, we hypothesized that their proteome may also differ specifically in their expression pattern, protein interaction pathways and post-translational modifications (PTM). We performed this study using 42 AML patients diagnosed for various cytogenetic abnormalities based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MS) and MSMS tandem MS. We could identify signi. cant differences in the proteome and PTM of peptides, later confirmed by other methods, between cytogenetic groups. The interactome analysis based on computational bioinformatics reveals major regulating networks: MAPK8 and MYC for complex aberrant karyotype, TP53 for t(8; 21), TP53-MYC-PRKAC for 11q23 and JUN and MYC for Inv(16). Further, we analysed 42 MS spectra representative of hnRNPH1, calreticulin and hnRNPA2/ B1 in a peak explorer, which reveals a cytogenetic-specific PTM of beta-O-linked N-acetyl glucosamine (O-GlcNAc) of hnRNPH1 in AML patients with 11q23 translocation, an acetylation of calreticulin in t(8; 21) translocation and methylation of hnRNPA2/ B1 in patients with translocations of t(8; 21) and inv(16). This report may lead to a new thinking about AML pathogenesis, as differences at PTM level could be used to distinguish different subtypes of AML.
机构:Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England
Cristea, IM
Gaskell, SJ
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机构:Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England
Gaskell, SJ
Whetton, AD
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机构:
Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, EnglandUniv Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England
机构:Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England
Cristea, IM
Gaskell, SJ
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机构:Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England
Gaskell, SJ
Whetton, AD
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机构:
Univ Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, EnglandUniv Manchester, Dept Biomol Sci, Leukaemia Res Fund Proteom Facil, Manchester M60 1QD, Lancs, England